1. HPV and cervical screening Test of cure
Dr Matt Hewitt

2. Cervical cancer in Ireland – key statistics
9th most frequently diagnosed cancer in women (278)
12th most common cause of cancer death in women (103)
Average age diagnosis - 46 years
Average age death - 56 years
Survival in Ireland is slightly lower than the European average.
The trends in mortality since 1978 show an increase of 1.5% per year.
Ref: National Cancer Registry Ireland

3. Key points – prevention of deaths from cervical cancer
Primary prevention
Vaccination
Secondary prevention
Cervical cytology
CervicalCheck screening programme
Early Diagnosis
Down staging of cancers at diagnosis
Agreed assessment and referral for women with symptoms

4. CERVIX SQ – squamous epithelium COL – Columnar epithelium SQ COL COL

6. Acidic vagina
Metaplasia

7. External os
Glandular epithelium
(Ectropion)
New Sq Col Jun
Transformation zone
Area of metaplasia
Native Sq Col Jun

8. HPV HPV types in cervical cancer
This graph shows the cumulative percentages of cervical cancer cases attributed to the most frequent HPV genotypes. In Europe and North America, types 16 and 18 together account for 71.5 per cent of all cervical cancer cases.1
The distribution of HPV types varies within countries and between regions. However, HPV 16 and HPV 18 are the first and second most common types in all regions, with some variation in their distribution.
Reference:
1. Muñoz N et al. Int J Cancer 2004; 111: 278–85.

9. Acidic vagina
Metaplasia
Acidic vagina
Dysplasia

11. Natural history of HPV infection
Transmission by sex
Lifetime risk 80% - most within 18 months
Exposure
Transient
Most resolve within 18 months
Infection
Less than 20% persist
No antibodies detectable
Persistence
Virus integrates into host DNA
Malignant Transformation
Loss of tumour suppressor gene E2
Uncontrolled cells division
CIN

12. Natural history of CIN
Observe Treat
(LLETZ)

13. Metaplasia
Cancer
CIN I
CIN II
CIN III

14. Use of HPV in screening
In the management of women with low grade sears
In the follow up of women who have had treatment
Future use of HPV in screening
HPV types in cervical cancer
This graph shows the cumulative percentages of cervical cancer cases attributed to the most frequent HPV genotypes. In Europe and North America, types 16 and 18 together account for 71.5 per cent of all cervical cancer cases.1
The distribution of HPV types varies within countries and between regions. However, HPV 16 and HPV 18 are the first and second most common types in all regions, with some variation in their distribution.
Reference:
1. Muñoz N et al. Int J Cancer 2004; 111: 278–85.

15. Low grade smears Very common Fill the colposcopy clinic with patients
Majority of low grade CIN will resolve spontaneously
Low grade CIN natural response to HPV infection
Patient anxiety
Cost
How to overcome these problems?
Use of HPV in low grade disease in colposcopy
Use of HPV in primary care
HPV types in cervical cancer
This graph shows the cumulative percentages of cervical cancer cases attributed to the most frequent HPV genotypes. In Europe and North America, types 16 and 18 together account for 71.5 per cent of all cervical cancer cases.1
The distribution of HPV types varies within countries and between regions. However, HPV 16 and HPV 18 are the first and second most common types in all regions, with some variation in their distribution.
Reference:
1. Muñoz N et al. Int J Cancer 2004; 111: 278–85.

17. Future screening protocols
Incorporate HPV in primary care screening
If Low grade smear and negative HPV avoid colp referral
Advantages
Cost saving
Reduced anxiety in colposcopy referral
Avoid unnecessary treatment
HPV types in cervical cancer
This graph shows the cumulative percentages of cervical cancer cases attributed to the most frequent HPV genotypes. In Europe and North America, types 16 and 18 together account for 71.5 per cent of all cervical cancer cases.1
The distribution of HPV types varies within countries and between regions. However, HPV 16 and HPV 18 are the first and second most common types in all regions, with some variation in their distribution.
Reference:
1. Muñoz N et al. Int J Cancer 2004; 111: 278–85.
Disadvantage
Counselling women about HPV infection

18. Options for follow-up after treatment
Cumulative incidence of CIN3+
Sensitivity of cytology is low with high false negatives
Traditional schedules Compensate by repeated smears – annual for ten years
HPV test with cytology has negative predictive value of> 90%
Dillner, J. et al. BMJ 2008

19. Follow-up after treatment
6 month smear at Colposcopy
12 month smear
24 month smear
36 month smear
48 month smear
60 month smear
72 month smear
84 month smear
96 month smear
120 month smear
Routine Recall
Traditional
strategy
6 Months HPV and Smear
18 months HPV and Smear
Discharge to routine screening if double negative
New strategy

21. HPV 16 and 18

22. Advantages of introducing the vaccine
Reduced incidence of cervical cancer (adeno and squamous)
Reduced incidence of genital warts
Reduce the incidence of genital cancer
Reduced incidence of some head and neck cancers
Potential to stop the cervical cancer screening programme
Greater impact in developing countries where there is no cervical screening
HPV types in cervical cancer
This graph shows the cumulative percentages of cervical cancer cases attributed to the most frequent HPV genotypes. In Europe and North America, types 16 and 18 together account for 71.5 per cent of all cervical cancer cases.1
The distribution of HPV types varies within countries and between regions. However, HPV 16 and HPV 18 are the first and second most common types in all regions, with some variation in their distribution.
Reference:
1. Muñoz N et al. Int J Cancer 2004; 111: 278–85.

23. Disadvantages of introducing the vaccine
Cost
Only covers 70 – 75% of cervical cancers
?Increased promiscuity
Ethical issues of vaccination of teenage girls
Delivery to young girls – counselling issues
Decreased uptake of smears in screening programme
Future role of colposcopy services
Long term efficacy
Side effects
Bad publicity
HPV types in cervical cancer
This graph shows the cumulative percentages of cervical cancer cases attributed to the most frequent HPV genotypes. In Europe and North America, types 16 and 18 together account for 71.5 per cent of all cervical cancer cases.1
The distribution of HPV types varies within countries and between regions. However, HPV 16 and HPV 18 are the first and second most common types in all regions, with some variation in their distribution.
Reference:
1. Muñoz N et al. Int J Cancer 2004; 111: 278–85.

25. IMPACT OF VACCINE AND DURATION OF PROTECTION5 4
10 year protection
& no screening 3
MORTALITY FROM CERVICAL CANCER DEATHS (PER 100,000 PER YEAR)
Screening
& no vaccination 2
10 year protection
& screening
Lifelong
& no screening 1
Lifelong protection
& screening 10 20 30 40 50
TIME SINCE START OF VACCINATION PROGRAM

26. Thank You